Alpha-oxoglutarate inhibits the proliferation of immortalized normal bladder epithelial cells via an epigenetic switch involving ARID1A

Muhammad Shahid, Nicole Gull, Austin Yeon, Eunho Cho, Jooeun Bae, Hyun Seok Yoon, Sungyong You, Hana Yoon, Minjung Kim, Benjamin P. Berman, Jayoung Kim

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Interstitial cystitis (IC) is a chronic urinary tract disease that is characterized by unpleasant sensations, such as persistent pelvic pain, in the absence of infection or other identifiable causes. We previously performed comprehensive metabolomics profiling of urine samples from IC patients using nuclear magnetic resonance and gas-chromatography/mass spectrometry and found that urinary α-oxoglutarate (α-OG), was significantly elevated. α-OG, a tricarboxylic acid (TCA) cycle intermediate, reportedly functions to suppress the proliferation of immortalized normal human bladder epithelial cells. Here, we identified AT-rich interactive domain 1 A (ARID1A), a key chromatin remodeler, as being hypomethylated and upregulated by α-OG treatment. This was done through EPIC DNA methylation profiling and subsequent biochemical approaches, including quantitative RT-PCR and western blot analyses. Furthermore, we found that α-OG almost completely suppresses ten-eleven translocation (TET) activity, but does not affect DNA methyltransferase (DNMT) activity. Altogether, our studies reveal the potential role of α-OG in epigenetic remodeling through its effects on ARID1A and TET expression in the bladder. This may provide a new possible therapeutic strategy in treating IC.

Original languageEnglish
Article number4505
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - 1 Dec 2018

Fingerprint

Dive into the research topics of 'Alpha-oxoglutarate inhibits the proliferation of immortalized normal bladder epithelial cells via an epigenetic switch involving ARID1A'. Together they form a unique fingerprint.

Cite this